The role of platelets in sepsis

Sepsis, a dysregulated host immune response to an infection, is a major cause of morbidity and death worldwide. In this thesis we studied the contribution of platelets to the immune response during sepsis. Platelets are historically viewed as hemostatic cells, but the work in this thesis (as well as other publications) shows that platelets can also influence host immune responses during infection. In a cohort of 930 European sepsis patients and in 1160 Asian patients with gram negative sepsis, we show that reduced platelet counts are associated with increased mortality. We moreover show that platelets can contribute to the dysregulated host response in sepsis patients, independent of disease severity. In murine models of pneumonia derived sepsis, we also found that low platelet counts (after platelet depletion) increased mortality. Low platelets counts moreover impaired host defense against bacteria en impaired vascular integrity. Using several Knock-out mice and antibodies, we were able to identify that platelets use their receptors Glycoprotein(GP)VI and GPIbα to partly mediate this protective effect. Platelet Toll Like receptor signalling was however not involved. Additionally, the interaction between the coagulation system (specifically thrombin) and platelets can also aid in host defense against gram-negative bacteria. In conclusion, we have shown that platelets can modulate immune responses during sepsis, and from our results it has become clear that platelets are not solely hemostatic cells.